Method for selectively killing protein aggregate-containing cells, kit therefor, therapeutic drug for protein misfolding diseases and drug product for removing protein aggregates from blood product

Abstract

A method for selectively killing protein aggregate-containing cells, a kit thereof, a therapeutic agent for the protein misfolding disease, and an agent for removing a protein aggregate from a blood derivative are provided. The method for selectively killing cells according to one embodiment acts a fluorine-based alcohol or a compound represented by general formula (1) on cells as a compound for detecting a protein aggregate and selectively kills protein aggregate-containing cells.

What is claimed is: 
     
         1 . A method for selectively killing protein aggregate-containing cells comprising:
 treating cells with a molecular structure-modifying agent, the molecular structure-modifying agent containing a fluorine-based alcohol or a compound represented by general formula (1),   
       
         
           
           
               
               
           
         
         wherein, in general formula (1), a is 0 or 1, 
         when a is 1, then R 1  is a hydrogen atom and R 2  is a hydroxyl group, or R 1  is a hydroxyl group and R 2  is a hydrogen atom, 
         when a is 0, then R 2  is an oxygen atom forming a double bond together with a carbon atom, 
         R 3  is CH l Cl m F n , and l is an integer from 0 to 3, m and n are integers from 1 to 3, and l+m+n=3 is satisfied, 
         R 4  is CH s Cl t F u , and s is an integer from 0 to 3, t and u are integers from 1 to 3, and s+t+u=3 is satisfied. 
         l+s<6 is satisfied. 
       
     
     
         2 . The method for selectively killing protein aggregate-containing cells according to  claim 1 , wherein
 the fluorine-based alcohol is presented by a general formula RfCH 2 OH or RfRf′CHOH,   Rf and Rf′ present a perfluoroalkyl group having 1 to 10 carbon atoms, and Rf and Rf′ are different from each other or the same.   
     
     
         3 . The method for selectively killing protein aggregate-containing cells according to  claim 1 , wherein the fluorine-based alcohol is 1,1,1,3,3,3-hexafluoro-2-propanol. 
     
     
         4 . The method for selectively killing protein aggregate-containing cells according to  claim 1 , wherein a concentration of the fluorine-based alcohol or a compound represented by general formula (1) when treating the cells is in a range from 1 μM to 100 mM. 
     
     
         5 . A kit for selectively killing protein aggregate-containing cells comprising:
 a fluorine-based alcohol or a compound represented by general formula (1),   
       
         
           
           
               
               
           
         
         wherein, in general formula (1), a is 0 or 1, 
         when a is 1, then R 1  is a hydrogen atom and R 2  is a hydroxyl group, or R1 is a hydroxyl group and R 2  is a hydrogen atom, 
         when a is 0, then R 2  is an oxygen atom forming a double bond together with a carbon atom, 
         R 3  is CH l Cl m F n , and l is an integer from 0 to 3, m and n are integers from 1 to 3, and l+m+n=3 is satisfied, 
         R 4  is CH s Cl t F u , and s is an integer from 0 to 3, t and u are integers from 1 to 3, and s+t+u=3 is satisfied. 
         l+s<6 is satisfied. 
       
     
     
         6 . The kit for selectively killing protein aggregate-containing cells according to  claim 5 , wherein
 the fluorine-based alcohol is presented by a general formula RfCH 2 OH or RfRf′CHOH,   Rf and Rf′ present a perfluoroalkyl group having 1 to 10 carbon atoms, and   Rf and Rf′ are different from each other or the same.   
     
     
         7 . The kit for selectively killing protein aggregate-containing cells according to  claim 1 , wherein the fluorine-based alcohol is 1,1,1,3,3,3-hexafluoro-2-propanol. 
     
     
         8 . The kit for selectively killing protein aggregate-containing cells according to  claim 5 , wherein a concentration of the fluorine-based alcohol or a compound represented by general formula (1) when treating the cells is in a range from 1 μM to 100 mM. 
     
     
         9 . A therapeutic agent for a protein misfolding disease comprising:
 a fluorine-based alcohol or a compound represented by general formula (1),   
       
         
           
           
               
               
           
         
         wherein, in general formula (1), a is 0 or 1, 
         when a is 1, then R 1  is a hydrogen atom and R 2  is a hydroxyl group, or R 1  is a hydroxyl group and R 2  is a hydrogen atom, 
         when a is 0, then R 2  is an oxygen atom forming a double bond together with a carbon atom, 
         R 3  is CH l Cl m F n , and l is an integer from 0 to 3, m and n are integers from 1 to 3, and l+m+n=3 is satisfied, 
         R 4  is CH s Cl t F u , and s is an integer from 0 to 3, t and u are integers from 1 to 3, and s+t+u=3 satisfied. 
         l+s<6 is satisfied. 
       
     
     
         10 . The therapeutic agent for the protein misfolding disease according to  claim 9 , wherein
 the fluorine-based alcohol is presented by a general formula RfCH 2 OH or RfRf′CHOH,   Rf and Rf′ present a perfluoroalkyl group having 1 to 10 carbon atoms, and   Rf and Rf′ are different from each other or the same.   
     
     
         11 . The therapeutic agent for the protein misfolding disease according to  claim 9 , wherein the fluorine-based alcohol is 1,1,1,3,3,3-hexafluoro-2-propanol. 
     
     
         12 . An agent for removing a protein aggregate from a blood derivative comprising:
 a fluorine-based alcohol or a compound represented by general formula (1),   
       
         
           
           
               
               
           
         
         wherein, in general formula (1), a is 0 or 1, 
         when a is 1, then R 1  is a hydrogen atom and R 2  is a hydroxyl group, or R 1  is a hydroxyl group and R 2  is a hydrogen atom, 
         when a is 0, then R 2  is an oxygen atom forming a double bond together with a carbon atom, 
         R 3  is CH l Cl m F n , and l is an integer from 0 to 3, m and n are integers from 1 to 3, and l+m+n=3 is satisfied, 
         R 4  is CH s Cl t F u , and s is an integer from 0 to 3, t and u are integers from 1 to 3, and satisfied that s+t+u=3 is satisfied. 
         l+s<6 is satisfied. 
       
     
     
         13 . The agent for removing the protein aggregate from the blood derivative according to  claim 12 , wherein
 the fluorine-based alcohol is presented by a general formula RfCH 2 OH or RfRf′CHOH,   Rf and Rf′ present a perfluoroalkyl group having 1 to 10 carbon atoms, and   Rf and Rf′ are different from each other or the same.   
     
     
         14 . The agent for removing the protein aggregate from the blood derivative according to  claim 12 , wherein the fluorine-based alcohol is 1,1,1,3,3,3-hexafluoro-2-propanol.